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Background: Recent studies identify a significant number of treated hypothyroid patients who express dissatisfaction with their therapy. At present there are sufficient measures of thyroid function to enable the clinician to establish a diagnosis of thyroid disease with a high degree of sensitivity and specificity. The purpose of this study was to quantitate the use of a new and novel assessment of clinically relevant hypothyroid symptoms in the management of patients with thyroid disease and to identify a tool that could help clinicians to assess adequacy of LT4 treatment. Methodology: Unselected outpatients of the Thyroid Clinic of the North Shore University Hospital at Manhasset completed a questionnaire asking them to rate their physical symptoms related to thyroid disease as part of their standard care. This questionnaire consisted of 10 signs and symptoms. The questionnaire was collected from 198 control subjects, 241 subjects with primary hypothyroidism (under treatment), 113 euthyroid subjects (benign nodular thyroid disease), 73 previously hyperthyroid subjects (previously treated), and 27 subjects with thyroid cancer. A repeat questionnaire was obtained from 48 subjects with primary hypothyroidism (20%), 19 euthyroid subjects (17%), and 17 subjects previously hyperthyroid (23%). Data Analysis: The mean score for the sum of the signs and symptoms in the primary hypothyroid group with no medication change was 9.62 ± 1.29 for the initial questionnaire, and 10.04 ± 1.32 for the follow up questionnaire (not significant). For the primary hypothyroid patients requiring a medication change, at the time of the initial questionnaire the mean serum TSH was 12.86 ± 2.75 mcU/ml. Concurrently with the normalization of TSH, a statistically significant improvement in the sum of signs and symptoms mean score for this group was noted (16.32 ± 1.93 initial vs. 10.32 ± 1.46 after treatment to normalize TSH). Conclusion: The proposed newly devised hypothyroid scale correctly identified subjects with TSH elevation and clinical/subclinical hypothyroidism based on their clinical signs and symptoms. In this particular subset of patients, the hypothyroid symptom scale showed a statistically significant improvement in the sum of the signs and symptoms with the normalization of the subjects' thyroid function.

Summary Context Thyroid cancer survivors represent a unique population in which the potential long-term effects of brief periods of intentional thyroid hormone withdrawal and/or prolonged periods of iatrogenic hyperthyroidism on body weight and body mass were evaluated. Objectives The objectives of this study were to characterize body mass changes over several years in a cohort of thyroid cancer patients with iatrogenic hyperthyroidism and to compare these changes with the expected weight gain in age-matched healthy control populations. We also evaluated the possibility that the method of preparation [thyroid hormone withdrawal (THW) vs recombinant human TSH (rhTSH)] for radioactive iodine remnant ablation may be associated with differences in body mass at the time of the final follow-up. Design/Setting/Patients/Interventions A retrospective review identified 153 patients with thyroid cancer who underwent total thyroidectomy at one major medical centre. Of the 153 patients, 143 also had radioactive iodine remnant ablation: 70 after THW and 73 after rhTSH. Main Outcome Measures Change in weight and BMI at 1–2 and 3–5 years of follow-up points were examined. Annualized weight variation within the cohort was compared with age-matched population controls expressed in kilogram/year. Results Significant weight gain was noted for the full cohort after 3–5 years of follow-up as compared to baseline (76 ± 21 kg at baseline vs 79 ± 23 kg at 3–5 years of follow-up, P

Current management guidelines suggest that 6-12 months after total thyroidectomy and radioactive iodine remnant ablation (RAI-RA), patients with differentiated thyroid cancer should be re-evaluated with serum thyroglobulin (Tg) and neck ultrasonography to assess the efficacy of initial treatment and to guide subsequent management. However, if serum Tg levels can continue to decline for many years after RAI-RA, then an early assessment of response to therapy could lead to excessive evaluations and treatments in patients with low-level Tg values that are likely to resolve over time without additional therapies.Serum Tg concentrations in patients with differentiated thyroid cancer, who had been thyroidectomized (Tx), received RAI-RA, and who were receiving levothyroxine to suppress serum thyrotropin (suppressed serum Tg), were retrospectively analyzed. The study included 299 patients, 69% of whom were women with an overall median age of 46 years and who had a median follow-up of 7 years. The study was limited to patients who received no additional treatments beyond total Tx, RAI-RA, and levothyroxine therapy to suppress thyrotropin. The primary endpoints were the time required to achieve the lowest Tg (nadir Tg) and the time required to achieve a suppressed serum Tg1 ng/mL.The nadir -suppressed serum Tg was achieved by 6 months in 58% of the patients and by 12 months in 75% of the patients. The remaining 25% of patients required 18 months or longer to reach the nadir Tg. However, in the subgroup of patients that eventually reached a nadir suppressed serum Tg1 ng/mL (n=223 patients), this goal was achieved by 6 months in 81%, by no more than 12 months in 91%, and by no more than 18 months in 94%. In patients with a 6-month suppressed serum Tg of 1-5 ng/mL, 54% eventually developed a suppressed serum Tg of1 ng/mL without additional therapy.In patients selected for continued observation, serum Tg levels often continue to decline for several years after total Tx and RAI-RA. While a 6-12-month assessment of the response to initial therapy is useful in patient management, strong consideration should be given to continued observation without additional therapy in patients with well-differentiated thyroid cancer who have 6-month suppressed serum Tg values of 1-5 ng/mL without a structurally identifiable disease.

Thyroid cancer survivors represent a unique population in which the potential long-term effects of brief periods of intentional thyroid hormone withdrawal and/or prolonged periods of iatrogenic hyperthyroidism on body weight and body mass were evaluated.The objectives of this study were to characterize body mass changes over several years in a cohort of thyroid cancer patients with iatrogenic hyperthyroidism and to compare these changes with the expected weight gain in age-matched healthy control populations. We also evaluated the possibility that the method of preparation [thyroid hormone withdrawal (THW) vs recombinant human TSH (rhTSH)] for radioactive iodine remnant ablation may be associated with differences in body mass at the time of the final follow-up. DESIGN/SETTING/PATIENTS/INTERVENTIONS: A retrospective review identified 153 patients with thyroid cancer who underwent total thyroidectomy at one major medical centre. Of the 153 patients, 143 also had radioactive iodine remnant ablation: 70 after THW and 73 after rhTSH.Change in weight and BMI at 1-2 and 3-5 years of follow-up points were examined. Annualized weight variation within the cohort was compared with age-matched population controls expressed in kilogram/year.Significant weight gain was noted for the full cohort after 3-5 years of follow-up as compared to baseline (76 ± 21 kg at baseline vs 79 ± 23 kg at 3-5 years of follow-up, P0·01), which represented a 3·2% increase. Female and male patients with thyroid cancer experienced 0·46 and 0·94 kg/year gain in weight, respectively, which is similar or somewhat higher than previously published age-matched population controls (ranging from 0·23 to 0·34 kg/year). When expressed as per cent change and comparing the final weight to the pre-operative baseline, the rhTSH group experienced approximately a 1·7% increase in weight compared with the 3·9% increase seen with THW patients (P = 0·02). When expressed as kg/year change, the rhTSH cohort had 0·34 kg/year change compared with the 0·64 kg/year change seen in the thyroid hormone withdrawal patients (P = 0·02).In otherwise, healthy patients with differentiated thyroid cancer, significant weight gain occurred during the 3-5 years of follow-up despite ongoing thyrotropin suppression. The data suggest that mild iatrogenic hyperthyroidism does not promote weight loss or prevent ageing-related weight gain. Greater weight gain was seen in patients prepared for radioactive remnant ablation with THW than with rhTSH.

A risk-adapted approach to management of thyroid cancer requires risk estimates that change over time based on response to therapy and the course of the disease. The objective of this study was to validate the American Thyroid Association (ATA) risk of recurrence staging system and determine if an assessment of response to therapy during the first 2 years of follow-up can modify these initial risk estimates.This retrospective review identified 588 adult follicular cell-derived thyroid cancer patients followed for a median of 7 years (range 1-15 years) after total thyroidectomy and radioactive iodine remnant ablation. Patients were stratified according to ATA risk categories (low, intermediate, or high) as part of initial staging. Clinical data obtained during the first 2 years of follow-up (suppressed thyroglobulin [Tg], stimulated Tg, and imaging studies) were used to re-stage each patient based on response to initial therapy (excellent, acceptable, or incomplete). Clinical outcomes predicted by initial ATA risk categories were compared with revised risk estimates obtained after response to therapy variables were used to modify the initial ATA risk estimates.Persistent structural disease or recurrence was identified in 3% of the low-risk, 21% of the intermediate-risk, and 68% of the high-risk patients (p 0.001). Re-stratification during the first 2 years of follow-up reduced the likelihood of finding persistent structural disease or recurrence to 2% in low-risk, 2% in intermediate-risk, and 14% in high-risk patients, demonstrating an excellent response to therapy (stimulated Tg 1 ng/mL without structural evidence of disease). Conversely, an incomplete response to initial therapy (suppressed Tg1 ng/mL, stimulated Tg10 ng/mL, rising Tg values, or structural disease identification within the first 2 years of follow-up) increased the likelihood of persistent structural disease or recurrence to 13% in low-risk, 41% in intermediate-risk, and 79% in high-risk patients.Our data confirm that the newly proposed ATA recurrence staging system effectively predicts the risk of recurrence and persistent disease. Further, these initial ATA risk estimates can be significantly refined based on the assessment of response to initial therapy, thereby providing a dynamic risk assessment that can be used to more effectively tailor ongoing follow-up recommendations.

In December 2007, the USFDA approved recombinant human thyroid stimulating hormone (rhTSH) for radioiodine remnant ablation after total thyroidectomy in patients with well-differentiated thyroid cancer without evidence of metastatic disease. Because previously undetected radioactive iodine (RAI)-avid metastatic lesions can be identified during remnant ablation, we sought to determine if rhTSH-stimulated uptake of RAI into these incidentally discovered metastases is associated with a significant therapeutic (tumoricidal) effect.This retrospective review describes the clinical outcome of 84 well-differentiated thyroid cancer patients in whom RAI-avid lesions outside the thyroid bed were first identified at the time of RAI remnant ablation (64 rhTSH stimulated, 20 thyroid hormone withdrawal [THW]) on either the diagnostic (63/84, 75%) or posttherapy (21/84, 25%) whole body scan (76 with locoregional metastasis only and 8 with pulmonary uptake). Following ablation, patients were classified as having either no evidence of disease or persistent disease on the basis of subsequent diagnostic whole body RAI scans, stimulated thyroglobulin, and cross-sectional imaging studies.Despite having RAI-avid metastatic disease identified outside the thyroid bed at the time of initial ablation, 70% (45/64) of rhTSH-assisted patients and 55% (11/20) of the THW group had no evidence of disease at a median of 2.7 years following the initial RAI ablation (p = 0.159). THW and rhTSH-stimulated RAI ablation had similar efficacy in eliminating RAI-avid locoregional metastases (42/60, 70% of rhTSH and 10/16, 63% of THW, p = 0.65) and pulmonary metastases (3/4, 75% of rhTSH and 1/4, 25% of THW, p = 0.41).Preparation with either rhTSH or THW in this retrospective study appears to have similar therapeutic (tumoricidal) effects on small volume RAI-avid metastatic disease incidentally discovered at the time of ablation in both locoregional lymph nodes and pulmonary parenchyma.

Recent studies have confirmed that radioactive iodine therapy after recombinant human TSH (rhTSH) stimulation effectively ablates the normal thyroid remnant. However, no published study has determined the effectiveness of rhTSH preparations on the important endpoint of disease recurrence. Methods: Disease recurrence was retrospectively assessed a median of 2.5 y after radioiodine remnant ablation (RRA) in 394 consecutive thyroid cancer patients (93% papillary, 71% female, 47 ± 15 y old [mean ± SD], median 131I dose of 3,996 MBq [108 mCi]). Results: Similar rates of clinically evident disease recurrence (4% rhTSH vs. 7% thyroid hormone withdrawal [THW], P = not statistically significant) and residual thyroid bed uptake without other evidence of persistent disease (4% rhTSH vs. 7% THW, P = not statistically significant) were seen in the 320 patients undergoing rhTSH-assisted RRA and the 74 patients prepared for RRA by THW. When the definition of no clinical evidence of disease included a suppressed thyroglobulin level of less than 1 ng/mL and a stimulated thyroglobulin level of less than 2 ng/mL, rhTSH-assisted RRA was associated with significantly higher rates of no clinical evidence of disease (74% rhTSH vs. 55% THW, P = 0.02) and significantly lower rates of persistent disease (19% rhTSH vs. 32% THW, P = 0.02) than was RRA after THW. Patients selected for rhTSH-assisted RRA were older (48 ± 15 vs. 44 ± 15 y, P = 0.03) and received a slightly higher administered activity of 131I (median, 4,033 MBq [109 mCi] vs. 3,811 MBq [103 mCi], P = 0.01) but did not differ with respect to sex, histology, disease stage, or mean time to recurrence (19 ± 9 mo for rhTSH vs. 20 ± 16 mo for THW). Conclusion: rhTSH-assisted RRA is associated with rates of clinically evident disease recurrence and persistent uptake in the thyroid bed that are similar to those for traditional THW.